Metagenomi's Therapeutic Advancements: Progress and Upcoming Milestones

Metagenomi, Inc. (Nasdaq: MGX), a precision genetic medicines company, has made significant strides across its therapeutic pipeline, as outlined in a recent update. The company's progress in hemophilia A, secreted protein deficiencies, and cardiometabolic programs has positioned it well to advance its potentially curative therapies toward clinical trials. Here, we highlight the key advancements and anticipated milestones for Metagenomi's therapeutic portfolio.



Hemophilia A Program (MGX-001)

Metagenomi's lead program, MGX-001, targets hemophilia A, a genetic bleeding disorder affecting approximately 26,500 patients in the US and over 500,000 globally. In 2024, the company achieved sustained Factor VIII (FVIII) activity in an ongoing nonhuman primate (NHP) study over more than 16 months of follow-up. This durability is a critical milestone for a one-time curative treatment, as it demonstrates the potential for long-lasting effects with a single administration.

In 2025, Metagenomi plans to finalize the ongoing NHP durability study, continue Investigational New Drug (IND) enabling efforts, and hold Pre-IND/ ex-US regulatory meetings to support IND/ Clinical Trial Application (CTA) submissions. This will pave the way for the company to advance MGX-001 into first-in-human studies in 2026.

Additionally, Metagenomi achieved higher FVIII activity at similar integration rates with a bioengineered MGX-001 FVIII construct compared to a wild-type FVIII construct in rodent studies. This suggests that the bioengineered construct may enable therapeutic FVIII activity at lower AAV doses, with potential safety benefits.

Secreted Protein Deficiency Platform

Metagenomi's approach to secreted protein deficiencies leverages the albumin approach used in MGX-001, which could open up new therapeutic opportunities for various genetic disorders. In 2024, the company identified targets for wholly-owned therapeutic programs in secreted protein deficiencies and plans to demonstrate NHP proof-of-concept for the lead target in 2025.

In 2026, Metagenomi anticipates nominating a Development Candidate for the lead secreted protein deficiency target, bringing the program closer to clinical trials. The market for secreted protein deficiency therapies is currently underserved, with limited treatment options available. Metagenomi's progress could create new market segments and attract significant investment.

Cardiometabolic Programs (Ionis Collaboration)

Metagenomi's partnership with Ionis Pharmaceuticals focuses on cardiometabolic indications, including transthyretin (TTR) for transthyretin amyloidosis and angiotensinogen (AGT) for refractory hypertension, as well as two undisclosed programs in significant cardiometabolic indications. In 2024, the company advanced all four Wave 1 Ionis collaboration programs to lead optimization and achieved in vivo proof-of-concept in rodents across all programs.

In 2025, Metagenomi plans to nominate one to two Development Candidates from the Wave 1 Ionis collaboration development programs and disclose remaining therapeutic indications in large cardiometabolic indications for the remaining development programs. This will help Metagenomi expand its pipeline and explore new therapeutic areas.

Metagenomi's progress across its therapeutic portfolio demonstrates the company's commitment to developing curative therapeutics for patients with unmet medical needs. The company's innovative gene editing approach, leveraging metagenomics-derived tools, sets it apart from competitors in the biotech sector. As Metagenomi continues to advance its pipeline, investors can expect to see significant value creation and market impact in the coming years.